Background. According to the Centers for Disease Control and Prevention, there were over 55,000 new HIV infections identified in the United States in 2006, and >50% were among men who report having sex with other men (MSM) (CDC, 2008). Substance use, in particular crystal methamphetamine and other club drugs (e.g., ecstasy, GHB, etc.) are highly associated with HIV sexual risk behavior and HIV infection among MSM. The use of the antiretrovirals tenofovir emtricitabine as pre-exposure prophylaxis (PrEP) is a novel biomedical HIV prevention strategy to help decrease HIV spread. Recent trials in HIV-uninfected men and women have demonstrated that PrEP is safe and well-tolerated, and data from a multinational randomized controlled trial of daily oral PrEP among 2,499 MSM were recently released, and show a significant decrease in HIV acquisition (Grant, Lama et al. 2010). Although harm reduction strategies such as needle exchange programs have been shown to decrease HIV infection among injection drug users (IDUs), it is unclear how PrEP will be utilized among MSM who use club drugs and engage in HIV sexual risk behavior. Overview of project. We propose to conduct qualitative interviews (phase 1) and a larger quantitative assessment (phase 2) among HIV-uninfected MSM who report recent club drug use and concurrent sexual risk (in the last 3 months) to gain a better understanding of the facilitators and barriers to PrEP implementation in this high risk group. All participants will be recruited from bars, nightclubs, and dance clubs in the Boston area that are known to attract gay and bisexual men and other MSM where club drug use is occurring. The phase 1 qualitative interviews will be conducted among 40 HIV-uninfected MSM to understand the potential factors surrounding PrEP acceptability, intent to use, and perceived ability to take PrEP among MSM with varied levels of club drug use who are at risk for HIV. We will rapidly analyze these data to inform and strengthen questions for the larger quantitative survey assessment (phase 2). In phase 2, Date-Time-Venue sampling will be used to recruit a random sample of 375 MSM (allowing for a 20% attrition from their recruitment venue to their in person assessment visit, yielding 300 total for the phase 2 assessment) from a variety of venues (bars, night clubs, dance clubs) in the greater Boston area. Of these 300 MSM, 50% will meet DSM-IV criteria for abuse/dependence of a given club drug and the other 50% will be those who have reported recent club drug use, but do not meet criteria for abuse/dependence (i.e., infrequent users). The lessons learned will provide key insights in the development of interventions to enhance PrEP adoption and utilization in this high-risk subpopulation of MSM.